Microglia are currently considered to be the main representatives of myeloid cells in the central nervous system (CNS) and perform a number of homeostatic functions. In response to damaging effects and changes in the CNS, microglia are activated and can perform both neuroinflammatory and neuroprotective roles. A number of studies indicate that chronic activation of microglia contributes to the development of demyelinating diseases. This review examines the contribution of microglia to the development and progression of multiple sclerosis, analyses its involvement in the demyelination process, and discusses potential therapeutic approaches aimed at modulating its activity.

   Objective: to evaluate the prognostic value of the THRIVE scale in patients aged 60 years and older with ischemic stroke (IS) after intravenous thrombolysis with Fortelyzin® (INN/chemical name – recombinant protein containing the amino acid sequence of staphylokinase; SuperGene LLC, Russia) compared to alteplase, based on a retrospective analysis of the results of the FRIDA randomised clinical trial.

   Material and methods. Patients (n = 336) were randomly assigned to either the Fortelyzin group (n = 168) or the alteplase group (n = 168). There were 124 patients (74 %) aged 60 years or older in the Fortelyzin group and 123 patients (73 %) in the alteplase group, and these patients were included in the analysis presented. Patients aged 60 years and older were also divided into two groups according to their modified Rankin scale (mRS) score on day 90: a group with a good functional outcome (mRS 0–2) and a group with an unfavourable functional outcome (mRS 3–6). The THRIVE scale was used to predict outcomes after treatment with Fortelyzin or alteplase. AUC values were then calculated. AUC ROC values were compared using the DeLong criterion.

   Results. For all-cause mortality at day 90, the predicted AUC value on the THRIVE scale was 0.8 (0.71–0.9) in the Fortelyzin group and 0.76 (0.66–0.87) in the alteplase group (p = 0.57). For adverse functional outcomes, the AUC value was 0.73 (0.64–0.82) in the Fortelyzin group and 0.79 (0.71–0.87) in the alteplase group (p = 0.36).

   Conclusion. The study confirmed the high predictive value of the THRIVE scale for predicting mortality and adverse outcomes in patients aged 60 years and older with IS after treatment with Fortelyzin and alteplase.

   Intravenous thrombolysis is the main method of reperfusion therapy for patients with ischemic stroke (IS) within the first 4.5 hours of symptom onset.

   Objective: to evaluate the clinical results of intravenous reperfusion therapy with a domestic thrombolytic drug, non-immunogenic staphylokinase (Fortelyzin®, SuperGene LLC, Russia), in patients with acute ischemic stroke (AIS) in the age group over 80 years in comparison with alteplase.

   Material and methods. Data from the hospital registry of patients over 80 years of age with AIS who were treated at the Penza G.A. Zakharin City Clinical Hospital No. 6 from January 2021 to April 2025 are presented. All patients underwent analysis of clinical, laboratory, and instrumental data in accordance with the procedure for providing medical care to patients with acute ischemic stroke and the reperfusion therapy protocol. The non-immunogenic staphylokinase group included 64 patients aged 80 to 94 years with AIS, and the alteplase group included 64 patients aged 80 to 96 years. The severity of neurological deficit according to the NIHSS upon admission was 13 points on average (from 5 to 23 points) in the non-immunogenic staphylokinase group and 12 points (from 5 to 23 points) in the alteplase group. No subsequent mechanical thromboembolectomy was performed. Safety criteria were the number of haemorrhagic transformations according to the Heidelberg classification and all-cause mortality at 90 days. The criterion for the effectiveness of thrombolytic therapy was the number of patients with good functional recovery (0–2 points on the modified Rankin scale – MRS) on day 90. Statistical processing of the results was performed using Microsoft Office.

   Results. In the non-immunogenic staphylokinase group, parenchymal haematoma (PH) type 1 was observed in two patients (3 %), and PH type 2 in five patients (8 %). In the alteplase group, type 1 PH was observed in two patients (3 %; p = 1.00), and type 2 PH was observed in four patients (6 %; p = 0.63). No significant differences in mortality on day 90 were found between the groups (34 % vs 47 %; p = 0.10). Good functional recovery (MRS 0–2 points) on day 90 was observed in 22 (34 %) patients in the non-immunogenic staphylokinase group and in 16 (25 %) patients in the alteplase group (p = 0.25).

   Conclusion. Thrombolytic therapy with non-immunogenic staphylokinase in elderly patients with AIS tends to have a higher probability of improving functional outcomes compared with alteplase and a comparable safety profile.

   Timely diagnosis of multiple sclerosis (MS) and early initiation of pathogenetic therapy are associated with a more favourable course of the disease and a lower degree of disability.

   Objective: to analyse the structure, causes and consequences of late diagnosis of MS among patients at the Russian Centre of Neurology and Neuroscience.

   Material and methods. The study included 125 patients with MS, clinically isolated syndrome (CIS) and radiologically isolated syndrome (RIS) who were referred for outpatient admission at the Russian Centre of Neurology and Neuroscience between October 2023 and March 2025. The duration of diagnosis and the time from disease onset to diagnosis, the reasons for delayed diagnosis and the correlation between delayed diagnosis and the degree of disability according to the Expanded Disability Status Scale (Expanded Disability Status Scale, EDSS) were determined, and a comparison was made with data from the Russian registry of patients with MS and data from foreign studies.

   Results. The median time to diagnosis was 10.0 [2.0; 42.8] months, and the mean time was 38.3 ± 69.7 months. The mean time between onset and brain magnetic resonance imaging was 29.9 ± 70.8 months, with a median of 5.0 [0.0; 23.8]. The frequency of delayed diagnosis of MS was 67.7 % (65/96). The mean EDSS score at the time of diagnosis was 2.6 ± 1.2 points. A statistically significant direct correlation was established between late diagnosis and a higher degree of disability on the EDSS scale (ρ = 0.331; p = 0.001).

   Conclusion. Late diagnosis of MS is associated with a higher degree of disability on the EDSS scale. The introduction of standard diagnostic deadlines for MS into clinical guidelines may help to reduce the frequency of delayed diagnosis and decrease the disability associated with late treatment initiation in patients.

   Headache remains one of the major public health problems worldwide. Assessing the prevalence and structure of headaches is a fundamental step towards the effective organisation of medical care for patients with cephalalgia.

   Objective: to clarify the structure of primary headaches and clinical characteristics of migraine among patients attending outpatient clinics at neurological clinics.

   Material and methods. A cross-sectional study was conducted with an analysis of the electronic medical records of patients who visited the Consultative and Diagnostic Department (CDD) of the Russian Center of Neurology and Neuroscience (RCNN) with diagnoses according to the International Classification of Diseases, 10^th Revision (ICD-10): G43 (Migraine) and G44 (Other headache syndromes), verified according to the criteria of the International Classification of Headache Disorders, 3rd revision (ICHD-3).

   Results. In 2022, 22,445 patients sought treatment at the CDD RCNN. Headache was diagnosed in 2,830 (12.6%) people: migraine in 1,325 (46.82 %), tension-type headache (TTH) – in 1,147 (40.53 %), trigeminal autonomic cephalalgia (TAC) – in 36 (1.27 %), other types of headache – in 322 (11.38 %). Most patients with headaches were women (71.55 %) aged 40.89 ± 18.12 years. Migraine without aura (G43.0) was detected in 52.61 %, migraine with aura (G43.1) – in 21.66 %, other migraine (G43.8) in 8.37 %, unspecified migraine (G43.9) in 15.93 %, and complicated migraine (G43.3) in 1.43 % of people. The average frequency of headaches was 17.60 ± 6.91 days per month. Rare episodic migraine was observed in 552 (37.05 %) patients, frequent episodic migraine in 282 (21.28 %) patients, and chronic migraine in 491 (41.67 %) patients. Most patients had a long history of the disease (17.10 ± 8.22 years), and about 70 % did not receive preventive treatment before contacting the RCNN.

   Conclusion. The study highlighted the problem of late referral of migraine patients for specialised care and the chronicity of the disease. Further systematic study of the prevalence and structure of headaches is important for the development of effective strategies for the diagnosis and treatment of primary cephalalgia.

   Objective: to study cognitive functions and the functional state of the vascular wall of the main arteries and microcirculation of the skin in middle-aged men with arterial hypertension (AH).

   Material and methods. Two hundred middle-aged men were studied. Neuropsychological examination and assessment of the emotional-affective sphere were carried out using standard methods. Vascular examination was performed using laser Doppler flowmetry (LDF), photoplethysmography (PPG), applanation tonometry (AT), and flow-dependent vasodilation (FDV) of the brachial artery (BA). Magnetic resonance imaging (MRI) was used to visualise changes in the brain.

   Results. Based on medical history data and office blood pressure (BP) measurements, two groups were identified: 108 men with AH (median age 51.0 [50.0; 51.0] years) and 92 without AH (median age 51.0 [50.0; 52.0] years). According to BP data, men with AH had higher arterial stiffness indices. According to PPG data, the calculated augmentation index (Alp75) was 6.8 % in the group of men with AH and 1.7 % in normotensive men (p < 0.05), the reflectivity index (RI) was 32.5 % and 29.2 % (p < 0.05), respectively, and the central systolic blood pressure in the proximal aorta and brachiocephalic arteries (Spa) was 134.5 and 119.5 mm Hg (p<0.0001), respectively; at the same time, the saturation index (SpO₂) was higher in men without AH – 94.9 % vs. 94.4 % in men with AH (p < 0.05). According to LDF data, no significant intergroup differences were found at the level of precapillary arterioles. According to FDV BA data, men with AH more often had vasodilator endothelial dysfunction (df = 1; χ² = 6.19; p < 0.05). According to the results of neuropsychological testing, men with AH had lower Mini-mental State
Examination scores (28.5 vs. 29 in men without AH; p < 0.05) and on the Benton Visual Retention Test (13 vs. 14 in men without AH; p < 0.05). According to brain MRI data, men with AH had grade I Fazekas scale white matter hyperintensity in 45 % of cases and grade II in 21 %. Also, among men with AH, enlargement of the cerebrospinal fluid spaces was significantly more common (df = 1; χ² = 4.8; p < 0.05).

   Conclusion. The first comprehensive study of the functional state of the vascular wall of the main arteries, skin microvessels and cognitive function in middle-aged men demonstrates greater stiffness of large arteries, indicating higher vascular stiffness and smooth muscle cell tone in terminal muscle arteries and distributive arterioles in men with hypertension than in men with normal blood pressure. Endothelial vasodilator dysfunction is more common among men with AH. Men with AH also have lower cognitive scores, mainly in the domain of visual memory.

   The results of the first analysis of life expectancy, mortality, and causes of death in patients with multiple sclerosis (MS) in the Republic of Bashkortostan (RB) are presented.

   Objective: to study life expectancy indicators and mortality patterns among MS patients in the RB.

   Material and methods. The assessment of indicators was based on data from the Republican Centre for MS (RCMS) registry at the G. G. Kuvatov Republican Clinical Hospital for the period 2005–2023. During this period, 2,967 patients (10,303 person-years) were treated at the RCMS, of whom 297 died. Life expectancy was assessed using the Gehan–Breslow test. Standardised mortality rates (SMR) were calculated. The causes of death were determined based on information from the Republican Medical Information and Analytical System of the RB.

   Results. In more than 70 % of cases, the cause of death may be related to MS and its complications. The overall SMR rate among patients was 1.92. The average life expectancy of MS patients is 19.1 years shorter than that of the general population. The median survival rate of patients was 32 years on average. The average life expectancy for women with MS was significantly higher than for men.

   Conclusion. In the RB, the presence of MS increases the risk of premature death and reduces the patient's life expectancy. The indicators studied in the republic reflect global patterns and trends.

   The most significant results in terms of efficacy in relapsing-remitting multiple sclerosis (MS) and primary progressive MS have been demonstrated for the drug ocrelizumab. Despite the significant role of randomised clinical trials in the study of the drug, the accumulation of experience in the real-world clinical practice of using ocrelizumab broadens the understanding of the drug's importance in the treatment of MS.

   Objective: to investigate the use of ocrelizumab in patients with MS living in the Yaroslavl region, as well as immunological predictors of ocrelizumab efficacy.

   Material and methods. The study included data from 107 patients diagnosed with MS according to the 2017 McDonald criteria (33 men and 74 women; median age – 42.1 [34.5; 49.7] years), with a disease duration of 10.3 [6.7; 16.9] years, and duration of therapy prior to starting ocrelizumab of 36.6 [25.9; 47.8] months. The efficacy and safety of therapy were analysed over 24 months of treatment.

   Results. A significant reduction in the frequency of exacerbations over 24 months of therapy was observed in the overall cohort of patients, from 0.53 to 0.10 per year (Z = 4.06; p < 0.001), and in MRI activity – from 1.38 to 0.09 new lesions on T2 images per year (Z = 3.88; p < 0.001). The overall NEDA-3 rate over 24 months of therapy was 76.64 %. It has been shown that a CD19⁺ level above 20 cells/ml before the second infusion of the drug may indicate the onset of disease activity in the following 18 months.

   Conclusion. The data obtained confirm the three-year efficacy and safety of ocrelizumab. The treatment has been shown to have a positive effect on NEDA-3 status.

   Objective: to evaluate the efficacy and safety of divozilimab, a humanised anti-CD20 monoclonal antibody, in patients with relapsing-remitting multiple sclerosis (MS) in real-world clinical practice.

   Material and methods. Divozilimab therapy was administered to 26 patients with MS. The observation period from the start of therapy was 5–7 months. The efficacy of therapy was assessed according to NEDA-3 criteria. As an additional laboratory indicator, the number of CD19⁺ and CD27⁺ cells was assessed in 10 patients by flow-cytometric immunophenotyping of peripheral blood lymphocytes. Safety monitoring consisted of assessing the frequency, severity and seriousness of adverse events (AEs) and the dynamics of laboratory parameters.

   Results. During the year prior to the start of divozilimab therapy, 24 out of 26 patients (92.3 %) experienced at least one clinical exacerbation, with some patients experiencing up to two or three exacerbations during the year. The median number of contrast-enhancing lesions on MRI was two. During the 5–7 months of therapy, there were no clinical exacerbations, progression of disability, or appearance of active lesions on MRI, indicating that all patients achieved NEDA-3 status. During treatment, three cases (5.8%) experienced mild infusion reactions. Two patients (7.7 %) subsequently experienced mild to moderate adverse events, which did not require discontinuation of therapy. None of the patients who underwent lymphocyte immunophenotyping had CD19⁺ and CD27⁺ cells (0 cells/μl).

   Conclusion. Short-term therapy with divozilimab demonstrated a favourable safety profile and efficacy according to NEDA-3 criteria. The absence of repopulation of CD19⁺, CD27⁺ cells indicates the efficacy of divozilimab B-cell lymphodepletion. Good tolerability and convenient administration underscore divozilimab application value in clinical practice. Longer follow-up and comparative studies with larger samples are needed to further investigate the safety and efficacy of its use.

   Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic hereditary disease of the small vessels of the brain caused by mutations in the NOTCH3 gene. We present the case of a 46-year-old patient whose CADASIL diagnosis was confirmed by genetic testing. In March 2023, the patient suffered an acute cerebrovascular accident with an infarction in the right midbrain tegmentum, developing diplopia when looking to the left, ataxia, followed by regression of symptoms. In June 2024, the patient's behaviour changed and weakness appeared in his right arm. An MRI revealed a subacute infarction in the basal structures of the left hemisphere of the brain, diffuse changes in the white matter of the temporal and frontal lobes, multiple small deep (lacunar) infarcts in the basal structures of both hemispheres of the cerebrum, the left thalamus, periventricular white matter, and corpus callosum. Genetic testing revealed a heterozygous mutation in the NOTCH3 gene – p.R169C (g528933696). A distinctive feature of clinical observation is the absence of migraine in patients with genetically confirmed CADASIL syndrome, as well as clinically pronounced cognitive and neuropsychological disorders.

   Immunotherapy using immune checkpoint inhibitors (ICIs) has demonstrated efficacy in treating a wide range of oncological diseases, but the use of this group of drugs is associated with the risk of developing serious immune-related adverse events (irAEs). Although relatively rare, neurological complications associated with ICI use are often life-threatening. The most common of these include myositis, myasthenia (with or with-out myositis), peripheral neuropathies, including Guillain–Barre syndrome, autoimmune encephalitis, myelitis, and demyelinating syndromes. This article presents five clinical observations of the development of neurological complications against the background of the use of anti-PD-1 inhibitors (pembrolizumab, nivolumab) as monotherapy or in combination with an anti-CTLA-4 inhibitor (ipilimumab). The cases presented were diagnosed with transverse myelitis, peripheral neuropathies meeting the diagnostic criteria for chronic inflammatory demyelinating polyneuropathy, and myositis, including in combination with myasthenia gravis. To relieve these conditions, glucocorticoids were used in the form of pulse therapy followed by oral administration, high-volume plasmapheresis, and cytostatic drugs. The treatment provided resulted in marked clinical improvement. The observations presented emphasise the importance of early diagnosis and effective treatment of irAEs as well as a multidisciplinary approach to the management of such patients. To date, the problems of selecting the optimal management strategy for irAEs and assessing the safety of subsequent ICIs use remain relevant and require further prospective studies.

   In addition to demonstrating the importance of a multidisciplinary approach, the purpose of presenting these observations is to raise awareness among neurologists about neurological immune-related adverse events caused by ICI therapy.

   The relevance of this task is determined by the fact that the widespread introduction of ICI into clinical practice for the treatment of various malignant neoplasms will inevitably lead to an increase in such cases in neurological practice, which predetermines the need for neurologists to be prepared to diagnose and manage such patients.

   In neighbouring borderline arterial zones of the brain (watershed), infarcts are possible due to insufficient blood supply. With the gradual development of occlusive lesions of the cerebral arteries in these areas, branched anastomotic networks form, capable of compensating for hypoperfusion. This review compiles material highlighting the formation of two external networks: leptomeningeal and durocortical, as well as three internal parenchymal networks: subependymal (including epithalamic), intrathalamic, and intrastriatal. The leptomeningeal network includes anastomoses between the branches of the posterior and anterior, posterior and middle cerebral arteries. The durocortical network is formed by all the dural branches from the vertebrobasilar system, the external and internal carotid arteries. The subependymal network is formed by the anterior and posterior choroidal arteries, thalamoperforating arteries, and perforating branches of the posterior communicating artery. The intratalamic and intrastriatal networks are formed by anastomoses between the striatal arteries and thalamoperforating vessels. Identification of these networks can play an important role in determining the stage of the disease, selecting treatment methods, and predicting clinical outcomes, as well as in ruling out possible complications.

   Body balance is maintained thanks to the coordinated work of the proprioceptive, visual and vestibular systems. Diabetes mellitus affects each of these systems, leading to the development of postural instability and an increased risk of falls in this group of patients. The high incidence of diabetic peripheral neuropathy and retinopathy has prompted detailed study of these conditions. It has been established that these conditions, leading to reduced visual acuity, sensory deficits and sensory ataxia, impair stability and increase the frequency of falls. At the same time, there is evidence of the potentially damaging effect of diabetes mellitus on the vestibular system with the development of subclinical vestibulopathy. Since the vestibular system plays an essential role in maintaining balance, timely detection of relevant disorders can be of considerable value in developing measures to prevent falls in this group of patients. Meanwhile, the prevalence and precise mechanisms of damage to the vestibular system in diabetes remain unclear, and the results of studies conducted in this area are characterised by high methodological and statistical heterogeneity, which makes it difficult to draw a single conclusion.

   Approximately 10 % of patients develop post-stroke epilepsy after stroke. Given the significant burden of stroke worldwide, post-stroke epilepsy is considered a serious problem for survivors. Post-stroke epilepsy is a major factor determining stroke prognosis and is associated with a high risk of mortality, adverse outcomes, and increased length of hospitalisation. Both early seizures occurring within the first 7 days after stroke onset and late seizures occurring more than 7 days after stroke onset are independent predictors of post-stroke epilepsy. The pathophysiological mechanisms underlying early and late seizures are different. The occurrence of post-stroke seizures is associated with a number of factors, including the type of stroke (ischemic or haemorrhagic), the location and size of the lesion, the severity of the disease, etc. Prognostic models help to assess the risk of epileptogenesis in patients after a stroke. The effectiveness of antiepileptic drugs in post-stroke epilepsy is higher than in other causes of focal epilepsy.

   Pain in the cervical spine is a widespread and socially significant problem. Its frequency increases with age, and its occurrence is associated with a complex of biological, psychosocial, and occupational risk factors. In most cases, the pain is benign. In unfavourable cases, chronic pain syndrome may develop. The key clinical step is to rule out specific causes of pain. The most common sources of pain in the cervical spine are facet joints, intervertebral discs, nerve roots (radiculopathy) or myofascial structures. The most important principle is to divide non-specific pain into acute and chronic, which determines further tactics. The article analyses current data on the pathogenesis, diagnostic approaches and principles of treatment of pain in the cervical spine. The possibilities of non-drug treatment methods, as well as drug therapy, primarily with non-steroidal anti-inflammatory drugs and centrally acting muscle relaxants, are discussed. The need for a multimodal and individualised approach aimed at pain relief, restoration of functional status and prevention of chronic pain syndrome is emphasised.

   The management of patients with acute vestibular vertigo (AVV) remains a difficult and pressing problem in modern medicine due to the variety of aetiological factors, the subjective nature of patient complaints, and the insufficient application of existing neurovestibular diagnostic algorithms in real clinical practice. Despite the large number of publications on the management of patients with AVV, certain issues regarding the examination and routing of patients remain unresolved to this day. Approximately a quarter of conditions manifested by AVV are caused by stroke or other life-threatening diseases, therefore emergency diagnosis is always necessary. Due to the insufficient informativeness of neuroimaging methods in patients with isolated vestibular vertigo, clinical diagnosis comes to the fore, requiring special training from doctors. Patients with peripheral causes of acute vestibular syndrome and vestibular migraine often do not receive fully effective treatment and recommendations for further rehabilitation in neurological hospitals, which makes an initially benign cause a trigger for chronic complaints of vertigo, leading to various functional disorders that slow down recovery, cause disability, and significantly reduce patients' quality of life. On 22 November 2025, a council of experts was held to discuss important issues related to the diagnosis, management and rehabilitation of patients with AVV, resulting in a proposed strategy for patient management.